Fostamatinib for the Treatment of Hospitalized Adults With Coronavirus Disease 2019: A Randomized Trial

Strich et al., Clinical Infectious Diseases, doi:10.1093/cid/ciab732, NCT04579393

Aug 2021

Double-blind RCT with 59 hospitalized COVID-19 patients requiring oxygen showing that adding fostamatinib to standard of care was safe and resulted in improved clinical outcomes compared to placebo, including faster recovery, fewer days in the ICU, and less supplemental oxygen needed, especially for those with severe or critical disease.

Standard of Care (SOC): SOC for COVID-19 in the study country, the USA, is very poor with very low average efficacy for approved treatments1. Only expensive, high-profit treatments were approved. Low-cost treatments were excluded, reducing the probability of treatment—especially early—due to access and cost barriers, and eliminating complementary and synergistic benefits seen with many low-cost treatments.

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risk of death, 67.8% lower, RR 0.32, p = 0.35, treatment 1 of 30 (3.3%), control 3 of 29 (10.3%), NNT 14, day 60.

risk of death, 85.9% lower, RR 0.14, p = 0.11, treatment 0 of 30 (0.0%), control 3 of 29 (10.3%), NNT 9.7, relative risk is not 0 because of continuity correction due to zero events (with reciprocal of the contrasting arm), day 28.

Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates

1. c19early.org, c19early.org/soc/usa.html.c19early.org/soc/usa.html.

Strich et al., 28 Aug 2021, Double Blind Randomized Controlled Trial, placebo-controlled, USA, peer-reviewed, mean age 55.6, 34 authors, study period 8 October, 2020 - 2 March, 2021, trial NCT04579393 (history). Contact: jeffrey.strich@nih.gov.

This Paper Miscellaneous All

Fostamatinib for the Treatment of Hospitalized Adults With Coronavirus Disease 2019: A Randomized Trial

Jeffrey R Strich, Xin Tian, Mohamed Samour, Christopher S King, Oksana Shlobin, Robert Reger, Jonathan Cohen, Kareem Ahmad, A Whitney Brown, Vikramjit Khangoora, Shambhu Aryal, Yazan Migdady, Jennifer Jo Kyte, Jungnam Joo, Rebecca Hays, A Claire Collins, Edwinia Battle, Janet Valdez, Josef Rivero, Ick Ho Kim, Julie Erb-Alvarez, Ruba Shalhoub, Mala Chakraborty, Susan Wong, Benjamin Colton, Marcos J Ramos-Benitez, Seth Warner, Daniel S Chertow, Kenneth N Olivier, Georg Aue, Richard T Davey, Anthony F Suffredini, Richard W Childs, Steven D Nathan

Clinical Infectious Diseases, doi:10.1093/cid/ciab732

Background: Coronavirus disease 2019 (COVID-19) requiring hospitalization is characterized by robust antibody production, dysregulated immune response, and immunothrombosis. Fostamatinib is a novel spleen tyrosine kinase inhibitor that we hypothesize will ameliorate Fc activation and attenuate harmful effects of the anti-COVID-19 immune response. Methods: We conducted a double-blind, randomized, placebo-controlled trial in hospitalized adults requiring oxygen with COVID-19 where patients receiving standard of care were randomized to receive fostamatinib or placebo. The primary outcome was serious adverse events by day 29. Results: A total of 59 patients underwent randomization (30 to fostamatinib and 29 to placebo). Serious adverse events occurred in 10.5% of patients in the fostamatinib group compared with 22% in placebo (P = .2). Three deaths occurred by day 29, all receiving placebo. The mean change in ordinal score at day 15 was greater in the fostamatinib group (-3.6 ± 0.3 vs -2.6 ± 0.4, P = .035) and the median length in the intensive care unit was 3 days in the fostamatinib group vs 7 days in placebo (P = .07). Differences in clinical improvement were most evident in patients with severe or critical disease (median days on oxygen, 10 vs 28, P = .027). There were trends toward more rapid reductions in C-reactive protein, D-dimer, fibrinogen, and ferritin levels in the fostamatinib group. Conclusion: For COVID-19 requiring hospitalization, the addition of fostamatinib to standard of care was safe and patients were observed to have improved clinical outcomes compared with placebo. These results warrant further validation in larger confirmatory trials. NCT04579393.

Supplementary Data Supplementary materials are available at Clinical Infectious Diseases online. Consisting of data provided by the authors to benefit the reader, the posted materials are not copyedited and are the sole responsibility of the authors, so questions or comments should be addressed to the corresponding author. Notes for this publication data collection and reporting. The authors also thank Henry Masur, MD (NIH Critical Care Medicine Department), for his support of this trial and thoughtful review of manuscript during preparation. Last, the authors thank the NHLBI's Division of Intramural Research (DIR), including the DIR's Office of the Clinical Director and Office of Biostatistical Research for providing the comprehensive support, oversight, and analysis needed to conduct this trial. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, NHLBI, NIAID, or National Institutes of Health Clinical Center. Financial support.

References

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DOI record: { "DOI": "10.1093/cid/ciab732", "ISSN": [ "1058-4838", "1537-6591" ], "URL": "http://dx.doi.org/10.1093/cid/ciab732", "abstract": "Abstract\n \n Background\n Coronavirus disease 2019 (COVID-19) requiring hospitalization is characterized by robust antibody production, dysregulated immune response, and immunothrombosis. Fostamatinib is a novel spleen tyrosine kinase inhibitor that we hypothesize will ameliorate Fc activation and attenuate harmful effects of the anti-COVID-19 immune response.\n \n \n Methods\n We conducted a double-blind, randomized, placebo-controlled trial in hospitalized adults requiring oxygen with COVID-19 where patients receiving standard of care were randomized to receive fostamatinib or placebo. The primary outcome was serious adverse events by day 29.\n \n \n Results\n A total of 59 patients underwent randomization (30 to fostamatinib and 29 to placebo). Serious adverse events occurred in 10.5% of patients in the fostamatinib group compared with 22% in placebo (P = .2). Three deaths occurred by day 29, all receiving placebo. The mean change in ordinal score at day 15 was greater in the fostamatinib group (-3.6 ± 0.3 vs -2.6 ± 0.4, P = .035) and the median length in the intensive care unit was 3 days in the fostamatinib group vs 7 days in placebo (P = .07). Differences in clinical improvement were most evident in patients with severe or critical disease (median days on oxygen, 10 vs 28, P = .027). There were trends toward more rapid reductions in C-reactive protein, D-dimer, fibrinogen, and ferritin levels in the fostamatinib group.\n \n \n Conclusion\n For COVID-19 requiring hospitalization, the addition of fostamatinib to standard of care was safe and patients were observed to have improved clinical outcomes compared with placebo. These results warrant further validation in larger confirmatory trials.\n \n \n Clinical Trials Registration\n Clinicaltrials.gov, NCT04579393.\n ", "author": [ { "affiliation": [ { "name": "Critical Care Medicine Department, National Institutes of Health Clinical Center , Bethesda, Maryland , USA" }, { "name": "United States Public Health Service Commissioned Corps , Rockville, Maryland , USA" } ], "family": "Strich", "given": "Jeffrey R", "sequence": "first" }, { "affiliation": [ { "name": "National Heart, Lung, and Blood Institute, National Institutes of Health , Bethesda, Maryland , USA" } ], "family": "Tian", "given": "Xin", "sequence": "additional" }, { "affiliation": [ { "name": "National Heart, Lung, and Blood Institute, National Institutes of Health , Bethesda, Maryland , USA" } ], "family": "Samour", "given": "Mohamed", "sequence": "additional" }, { "affiliation": [ { "name": "Advanced Lung Disease and Lung Transplant Program, Inova Fairfax Hospital , Falls Church, Virginia , 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"e0242400", "journal-title": "PLoS One", "key": "2023020110331268900_CIT0023", "volume": "15", "year": "2020" }, { "DOI": "10.1016/S2352-3026(20)30217-9", "article-title": "Haematological characteristics and risk factors in the classification and prognosis evaluation of COVID-19: a retrospective cohort study", "author": "Liao", "doi-asserted-by": "crossref", "first-page": "e671", "journal-title": "Lancet Haematol", "key": "2023020110331268900_CIT0024", "volume": "7", "year": "2020" } ], "reference-count": 24, "references-count": 24, "relation": {}, "resource": { "primary": { "URL": "https://academic.oup.com/cid/article/75/1/e491/6358811" } }, "score": 1, "short-title": [], "source": "Crossref", "subject": [], "subtitle": [], "title": "Fostamatinib for the Treatment of Hospitalized Adults With Coronavirus Disease 2019: A Randomized Trial", "type": "journal-article", "volume": "75" }

Late treatment
is less effective

Please send us corrections, updates, or comments. c19early involves the extraction of 100,000+ datapoints from thousands of papers. Community updates help ensure high accuracy. Treatments and other interventions are complementary. All practical, effective, and safe means should be used based on risk/benefit analysis. No treatment or intervention is 100% available and effective for all current and future variants. We do not provide medical advice. Before taking any medication, consult a qualified physician who can provide personalized advice and details of risks and benefits based on your medical history and situation. FLCCC and WCH provide treatment protocols.

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